Title: synNotch-programmed iPSC-derived NK cells usurp TIGIT and CD73 activities for glioblastoma therapy
Authors: Lupo KB, Yao X, Borde S, Wang J, Torregrosa-Allen S, Elzey BD, Utturkar S, Attalah Lanman N, McIntosh M., Matosevic S.
Journal/Publisher: Nature Communications
Summary (one paragraph that a layperson can understand): In this study, we developed genetically, engineered, tumor-responsive pluripotent stem cell-derived natural killer (NK) cells for immunotherapy of brain tumor (glioblastoma). These NK cells were engineered to target and block multiple elements, in a responsive manner, locally in the microenvironment of brain cancer and demonstrated potent anti-tumor effects and elimination of brain tumor growth in animal models of glioblastoma in vivo.
Significance (one paragraph that a layperson can understand): This study demonstrates, for the first time, efficacy of engineered stem cell-derived NK cells as novel immunotherapies for brain cancer. We not only demonstrated that co-targeting multiple elements of suppression of the immune system in brain cancer can enhance immune responses, but also that developing NK cells from pluripotent stem cells can serve as a robust new immunotherapeutic modality for this tumor.
Scholarly Impact (one paragraph that a layperson can understand): This study is the first example in the published literature of engineered pluripotent stem cell-derived NK cells designed to target multiple immune-suppressive mechanisms in brain cancer. It is a significant milestone for immunotherapy of brain tumors - an untreatable cancer - and represents a significant leap toward clinical advancement of brain tumor therapy with potentially off-the-shelf, potent cell-based therapies.